12 Oral Presentations
Our data support the development of a bivalent HBV-
HCV prophylactic vaccine that could be used to induce a
protective primary immunity to both HBV and HCV or as
a booster in individuals previously vaccinated against HBV,
to induce protective immunity to HCV.
HEV3
O-20
Indeterminate acute liver failure: it may be
Hepatitis E
P Manka1,2, L Bechmann1, JD Coombes2,
V Thodou1, M Schlattjan1, A Kahraman1,
W-K Syn2,3, F Saner4, G Gerken1, HA Baba5,
J Verheyen6, J Timm7 and A Canbay1 1Department of
Gastroenterology and Hepatology, University Hospital, University
Duisburg-Essen, Essen, Germany, 2The Institute of Hepatology,
Regeneration and Repair Group, Foundation for Liver Research,
London, UK, 3Barts Health NHS Trust, Liver Unit, London, UK,
4
Department of General, Visceral and Transplantation Surgery,
University Hospital, University Duisburg-Essen, Essen, Germany,
5
Institute of Pathology and Neuropathology, University Hospital,
University Duisburg-Essen, Essen, Germany, 6Institute of Virology,
University Hospital, University Duisburg-Essen, Essen, Germany,
7
D€
usseldorf University Hospital, Heinrich-Heine-University, Institute of
Virology, D€
usseldorf, Germany
BACKGROUND AND AIMS: In western countries hepatitis E
has long been regarded as rare imported infection from
endemic regions. Recent studies showed an increase of
hepatitis E seroprevalence among adults in central Europe.
Although hepatitis E can cause acute liver failure (ALF),
only few confirmed cases of hepatitis E virus (HEV) induced
ALF in Europe exist. This study aimed to evaluate the evi-
dence for acute hepatitis E infection in cases of indetermi-
nate ALF.
METHODS: Data from patients with ALF or acute hepati-
tis was acquired by retrospective analysis of case notes
and databases. Archived sera were tested for IgG anti-
HEV, IgM anti-HEV, and RNA (analytic sensitivity of
1 IU/ll).
RESULTS: Among 80 patients with ALF, 12 (15%) tested
positive for anti-HEV IgG. 64 (80%) patients tested nega-
tive for anti-HEV IgG, IgM and HEV RNA. Seven patients
(9%) with a positive result for anti-HEV IgG were anti-HEV
IgM and HEV RNA negative. In total eight patients (10%)
were tested positive for HEV RNA, with mixed serological
patterns (4 IgG positive, 4 IgG negative). and exhibited
signs of an acute hepatitis E infection after re-evaluation of
clinical, serological and RNA-data.
CONCLUSIONS: Acute hepatitis E is underestimated as a
cause of ALF in Germany. Serologic testing for IgG anti-
Journal of Viral Hepatitis © 2015 John Wiley & Sons Ltd, Vol 22 (Suppl. S2), June 2015, 1–18
HEV alone may be insufficient to exclude hepatitis E infec-
tion. RNA testing should be performed if ALF is suspected
and the etiology remains ambiguous.
HAV
O-21
Novel perspectives for Hepatitis A Virus therapy
resulting from comparative analysis of
Hepatitis C Virus and Hepatitis A Virus RNA
replication
K Esser-Nobis1, C Harak1, P Schult1, Y Kusov2 and
V Lohmann1 1Department of Infectious Diseases, University of
Heidelberg, Heidelberg, Germany, 2Institute of Biochemistry, University
of L€ubeck, L€
ubeck, Germany
Hepatitis A Virus (HAV) and Hepatitis C Virus (HCV) are
two positive-strand RNA viruses sharing a similar biol-
ogy but causing opposing infection outcomes, with HAV
always being cleared and HCV establishing persistence in
the majority of infections. To gain deeper insights into
determinants of replication, persistence and treatment,
we established a homogenous cell culture model allowing
a thorough comparison of RNA replication of both
viruses. By screening different human liver-derived cell
lines with subgenomic reporter replicons of HAV as well
as of different HCV genotypes, we found that Huh7_Lu-
net cells supported HAV and HCV RNA replication with
similar efficiency and limited interference between both
replicases. HAV and HCV replicons were similarly sensi-
tive to interferon, but differed in their ability to establish
persistent replication in cell culture. In contrast to HCV,
HAV replicated independently from microRNA-122 and
phosphatidylinositol 4-kinase IIIa and b (PI4KIII). Both
viruses were efficiently inhibited by cyclosporin A and
NIM811, a non-immunosuppressive analog thereof, sug-
gesting an overlapping dependency on cyclophilins for
replication. However, analysis of a broader set of inhibi-
tors revealed that, in contrast to HCV, HAV does not
depend on cyclophilin A, but rather on ATP-binding-cas-
sette-transporters and FK506 binding proteins. Finally,
silibinin but not its modified intravenous formulation,
efficiently inhibited HAV genome-replication in vitro, sug-
gesting oral silibinin as possible therapeutic option for
HAV infections.
CONCLUSION: We established a cell culture model enabling
comparative studies on RNA replication of HAV and HCV
in a homogeneous cellular background with comparable
replication efficiency. We thereby identified new host cell
targets and potential treatment options for HAV and set
the ground for future studies to unravel determinants of
clearance and persistence.
© 2015 The Authors